100 healthy medical students were studied with 24-h Holter monitoring for ST-segment evaluation. Six recordings (1.8% of males and 11.6% of females) contained at least one episode of horizontal or downsloping ST-segment depression of at least 0.1 mV or more and 1 min duration in the V-5-like lead. Since ST-segment elevations (in 73% of the recordings in the V-5-like lead, and in 40% in the V-2-like lead) and discordant (negative) T-waves associated with ST-segment depressions (in 31% of the recordings in the V-2-like lead) were commonly seen, these ECG findings have to be considered as nonspecific. During exercise tests using a protocol of maximal work load, not one of these healthy individuals displayed typical ST-segment depressions indicative of myocardial ischemia. Therefore, typical documented ST-segment alterations in Holter-ECG recordings should be used with caution when observed in individuals with suspected coronary heart disease, particularly when they are female.